pituitrin and 4-bromophenacyl-bromide

A mechanism by which vasopressin enhances phospholipase A2 activation in rabbit platelets was investigated. Stimulation of the platelets with vasopressin enhanced arachidonic acid liberation, as well as aggregation and ATP secretion in the presence of submaximal concentration of A23187, although vasopressin alone had no effect. The vasopressin-enhanced liberation was inhibited by p-bromophenacyl bromide, a phospholipase A2 inhibitor, and by genistein, a tyrosine kinase inhibitor. Though epinephrine also caused a similar enhancement of the liberation, this effect of epinephrine was insensitive to genistein. Staurosporine, a protein kinase C inhibitor, completely suppressed phorbol 12-myristate 13-acetate-enhanced arachidonic acid liberation, but suppressed the vasopressin-induced enhancement only slightly. These results suggest that vasopressin-enhanced phospholipase A2 activation may be regulated by a genistein-sensitive mechanism, most likely by a protein tyrosine kinase-mediated pathway, but not by guanine nucleotide-binding protein- or protein kinase C-mediated pathway.

Topics: Acetophenones; Adenosine Triphosphate; Alkaloids; Animals; Arachidonic Acid; Blood Platelets; Calcimycin; Drug Synergism; Epinephrine; Genistein; Isoflavones; Phospholipases A; Phospholipases A2; Platelet Aggregation; Protein Kinase C; Protein-Tyrosine Kinases; Rabbits; Staurosporine; Tetradecanoylphorbol Acetate; Vasopressins

The exposure of perfused rat livers to depolarizing concentrations of K+ (60 mM) by partial substitution of the NaCl in the medium with KCl induces glycogenolysis, respiratory changes and vasoconstriction. These responses were found to be inhibited 70-80% by 20 microM indomethacin and by 20 microM bromophenacyl bromide. This suggests that eicosanoids, namely prostaglandins, are involved in mediating these effects, and hence that the action of K+ involves primarily an effect on eicosanoid-producing cells (Kupffer and endothelial cells) within the liver. A 5 min pre-exposure of perfused livers to depolarizing concentrations of K+ (in the presence of indomethacin) was found to inhibit (by approx. 85%) the influx of Ca2+ induced by the co-administration of 10 nM glucagon and 10 nM vasopressin. A similar result was observed in isolated hepatocytes. The inhibition was probably not due to a decrease in the concentration of Na+ in the medium since the substitution of 80 mM NaCl with 80 mM choline chloride resulted in significantly less inhibition (30-40%). These results suggest that under these conditions the influx of Ca2+ in liver occurs through a pathway that is inhibited by high K+ concentration and/or a depolarization of the plasma membrane.

Topics: Acetophenones; Animals; Calcium; Glucagon; Indomethacin; Liver; Liver Glycogen; Oxygen Consumption; Potassium; Rats; Vasoconstriction; Vasopressins

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) stimulates glycogenolysis in perfused rat liver. The effect of TPA was blocked by indomethacin and bromophenacyl bromide. The effect of TPA on glucose output was transient in spite of the continuous presence of the phorbol ester in the perfusion medium. Addition of platelet activating factor (PAF) after the effect of TPA did not stimulate glycogenolysis. In contrast, vasopressin was able to stimulate glucose output under these conditions. Interestingly, as previously reported, PAF produced also transient stimulation of glycogenolysis; the addition of TPA after the effect of PAF had declined, was also unable to increase glucose output by the liver. It is suggested that both PAF and TPA stimulate hepatic metabolism through the generation of cyclooxygenase products.

Topics: Acetophenones; Animals; Female; Glucose; Indomethacin; Liver Glycogen; Perfusion; Phorbols; Phospholipases A; Platelet Activating Factor; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred Strains; Tetradecanoylphorbol Acetate; Vasopressins